The present inventor has previously reported the discovery that blood and other bodily fluids from normal individuals contain a significant number of autoantibodies, that, when treated with an oxidizing agent, become capable of binding self antigens. See, for example, the following publications:    McIntyre, J A. “The appearance and disappearance of antiphospholipid antibodies subsequent to oxidation-reduction reactions.” Thromb. Res. 2004; 114:579-87.    McIntyre, J A, Wagenknecht, D R, & Faulk, W P. “Autoantibodies unmasked by redox reactions.” J. Autoimmun 2005; 24:311-17.    McIntyre, J A, Wagenknecht, D R, & Faulk, W P. “Redox-reactive autoantibodies: Detection and physiological relevance.” Autoimm. Rev. 2006; 5:76-83.    McIntyre, J A, Chapman, J, Shavit, E, Hamilton, R L, DeKosky, S T. “Redox-reactive autoantibodies in Alzheimer's patients' cerebrospinal fluids: Preliminary studies.” Autoimmunity, 2007; 40:390-6.    McIntyre, J A, Hamilton, R L, DeKosky, S T. “Redox-reactive autoantibodies in cererebrospinal fluids.” Ann. N.Y. Acad. Sci. 2007; 1109: 296-302.    U.S. Patent Application Publication No. 2005/0260681 A!    and U.S Patent Application Publication No. 2005/0101016 A1.
In these publications, it was reported that blood from normal individuals contains a significant number of autoantibodies, in a wide variety of isotypes and specificities, but that these autoantibodies become detectible only when certain body fluids or blood are exposed to oxidation, by, for example an oxidizing agent or electric current, according to a method described therein. It was reported that samples such as blood, plasma, serum, breast milk, cerebrospinal fluid, and purified immunoglobulin fractions can be treated by oxidation and then assayed with a variety of self antigens and other types of antigens to identify masked autoantibodies that can be unmasked by oxidation. Autoantibodies that have been unmasked by oxidation include the following in Table 2:
TABLE 2Masked autoantibodies identified to date after redox conversion ofnormal plasma or IgG.Specificity AssayMethod of DetectionGlutamic acid decarboxylase (GAD)RIATyrosine phosphatase (IA-2)RIAAntiphospholipid antibodies:ELISAaPS, aPE, aCL, aPCLupus anticoagulant (LA)APTT, dRVVTAntinuclear antibodies (ANA)RELISA ®Anti-nucleolusimmunofluorescenceAnti-lamin, nuclear membranesimmunofluorescenceAnti-mitochondriaimmunofluorescenceAnti-GolgiimmunofluorescenceAnti-granulocyte, neutrophil,Flow Cytometry (FACS)monocyteAnti-B lymphocytesFACSAnti-myeloperoxidaseELISAAnti-tumor cell linesWestern blotAnti-trophoblastimmunofluorescenceAnti-factor VIIIELISAPlatelet factor 4/heparin complexELISAAnti-beta2-glycoprotein IELISARed Blood cellsOrtho Gel CardsRo/SS-AELISAAnti-human antigens*Invitrogen ProtoArray ®Table 2 abbreviations used:aCL, anticardiolipinaPC, antiphosphatidylcholineaPE, antiphosphatidylethanolamineaPS, antiphosphatidylserineAPPT, activated partial thromboplastin timedRVVT, dilute Russell's viper venom timeELISA, enzyme-linked immunosorbant assayRIA, radioimmunoassay*5,000-6,000 of 8,000 human antigens tested by microarray are recognized by redox-sensitive autoantibodies.
It has now been discovered that the binding specificity of monoclonal antibodies can be altered by similar treatments with an oxidizing agent or a direct electric current. This finding is significant, since monoclonal antibodies are typically intended to bind only a specific antigen. However, according to the method described herein, the spectrum of activity of a monoclonal antibody can be broadened to include antigens other than the specific antigen that the monoclonal antibody is intended to bind.